WO2010050604A1 - Objet tridimensionnel fabriqué par stéréolithographie et auquel un traitement de cytocompatibilité est appliqué - Google Patents

Objet tridimensionnel fabriqué par stéréolithographie et auquel un traitement de cytocompatibilité est appliqué Download PDF

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WO2010050604A1
WO2010050604A1 PCT/JP2009/068734 JP2009068734W WO2010050604A1 WO 2010050604 A1 WO2010050604 A1 WO 2010050604A1 JP 2009068734 W JP2009068734 W JP 2009068734W WO 2010050604 A1 WO2010050604 A1 WO 2010050604A1
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stereolithography
dimensional object
post
hours
cell
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PCT/JP2009/068734
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English (en)
Japanese (ja)
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幸士 生田
佳則 井上
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独立行政法人科学技術振興機構
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Priority to EP09823714.2A priority Critical patent/EP2351825B1/fr
Priority to US12/998,553 priority patent/US8845948B2/en
Publication of WO2010050604A1 publication Critical patent/WO2010050604A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C71/00—After-treatment of articles without altering their shape; Apparatus therefor
    • B29C71/02—Thermal after-treatment
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10—Processes of additive manufacturing
    • B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B29C64/124—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified
    • B29C64/129—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified characterised by the energy source therefor, e.g. by global irradiation combined with a mask
    • B29C64/135—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified characterised by the energy source therefor, e.g. by global irradiation combined with a mask the energy source being concentrated, e.g. scanning lasers or focused light sources
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y70/00—Materials specially adapted for additive manufacturing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/20—Material Coatings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0805—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation
    • B29C2035/0827—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation using UV radiation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C71/00—After-treatment of articles without altering their shape; Apparatus therefor
    • B29C71/04—After-treatment of articles without altering their shape; Apparatus therefor by wave energy or particle radiation, e.g. for curing or vulcanising preformed articles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/0094—Geometrical properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor
    • B29L2031/7532—Artificial members, protheses
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/24—Structurally defined web or sheet [e.g., overall dimension, etc.]

Definitions

  • the present invention relates to the field of solid freeform manufacturing method to which stereolithography belongs, the field of photocurable materials used therefor, and the technology of the field of imparting cytocompatibility of materials. It relates to an object that is detoxified with respect to cytocompatibility while in contact.
  • the micro stereolithography method is a fine processing technique capable of producing an arbitrary three-dimensional microstructure by irradiating a photocurable resin with a laser.
  • the present inventor Ikuta et al., Achieved the world's first three-dimensional resolution of 5 ⁇ m (see Non-Patent Document 1), and many studies have been developed thereafter (see Non-Patent Document 2).
  • nano stereolithography with submicron resolution has been developed.
  • application to the development of ⁇ -TAS and MEMS devices that perform chemical reaction and analysis in a fine channel has begun to be attempted (see Non-Patent Documents 3 to 5).
  • Non-Patent Documents 6 to 8 since the commercially available optical modeling resin is not biocompatible, there is a fundamental problem that it cannot be used for a device that directly contacts a living body or cells (see Non-Patent Documents 6 to 8). In order to solve this problem, the present inventors are not a research approach to develop a new photo-curing resin having biocompatibility and sufficient curing characteristics and curing accuracy. We challenged a research approach with more versatility and practicality to give cell compatibility to commercially available epoxy-based stereolithography resins that are stable. Conventionally, the following research exists as an application in which an optically shaped object directly contacts a cell or a living body.
  • the first research is a technique for avoiding photopolymerization initiators with high cytotoxicity and performing photo-fabrication using biodegradable polymers such as caprolactone and poly (propylene fumarate) as materials (Non-patent Document 8). ⁇ See 11). This method requires a resin synthesis process and a compounding process. Furthermore, since it aims to produce a biodegradable cell scaffold for regenerative medicine, it cannot be applied to the non-degradable device that is the purpose of this study.
  • the second study is a technique for producing a scaffold for cells using a hydrogel such as Polyethylene glycol (see Non-Patent Documents 7 and 13).
  • Non-Patent Document 14 Ikuta K, Hirotaro K. Real three dimensional microfabrication using stereolithography and metal molding. Proceedings of the IEEE Workshop on Microelectromechanical Systems, MEMS '93. 1993: 42-47. Bertsch A, Jigut S, Bernhard P, Renaud P.
  • Microstereolithography a Review. Mat. Res. Soc. Symp. Proc. 2003, LL1.1.1-LL1.1.13 Maruo S, Ikuta K, Koroji H. et al. Submicron manipulation tools drive by light in a liquid. Appl Phys Lett 2003; 82: 133-135. Kawata S, Sun HB, Tanaka T, Takada K. et al. Finer features for functional microdevices. Nature 2001; 412: 697-698. Maruo S, Ikuta K. et al. Submicron stereolithography for the production of freely mobile mechanism by using single-photon polymerization. Sensor Actuate A-phys 2002; 100: 70-76. Lu Y, Chen SC.
  • the three-dimensional object produced using the conventional stereolithography method is composed of monomers, oligomers, photopolymerization initiators, free radicals, which are included in the non-uniformity at the time of curing during the reaction and the photocurable material itself. It has been reported for some time that polyols and stabilizers show cytotoxicity (Patent Document 1). In addition, many biodegradable materials have been proposed as biocompatible materials for applications that contact a living body for a long period of time (Patent Document 2, Non-Patent Documents 10 and 12). As described above, the prior art has focused on producing a non-toxic material instead of detoxifying the material.
  • Patent Document 1 JP2003-10312A JP 2007-284550 A
  • the present inventors estimated from the above research results that the cytotoxicity of the optically shaped article is an uncured monomer or a photopolymerization initiator contained in the optically shaped article.
  • various “post cures” meaning that polymerization curing proceeds further after stereolithography suppresses cytotoxicity.
  • the method was examined. Three-dimensional objects formed by stereolithography are limited in the range of application as products due to their cytotoxicity. In general, when a toxic material is used for a product that comes into contact with a living body, an additional detoxification process must be applied.
  • an object of the present invention is to provide a three-dimensional structure to which cytocompatibility is imparted by detoxifying a three-dimensional object produced by an optical modeling method.
  • Cytocompatibility refers to the property of a material that is non-toxic to cells and does not adversely affect cell viability.
  • the technical solution means adopted by the present invention is: A microstructured three-dimensional object produced by a micro stereolithography method, wherein the cell is isolated and cultured at least in vitro, and is detoxified with respect to cell compatibility that allows contact culture on the object surface, Further, the detoxification is carried out by curing the object with ultraviolet rays and then setting it to at least the glass transition temperature of the object.
  • the molding material of the object is a three-dimensional object characterized in that the main material is molded from a photocurable material selected from the group consisting of acrylate, epoxy, acrylate / epoxy composite, and oxetane.
  • the transition point temperature is about 175 ° C. to 200 ° C., and the heating is performed for 6 hours to 24 hours.
  • the object has a portion in which any of x, y, and z of at least one part of the object is less than 1 mm and the temperature of the object exceeds at least the glass transition temperature of the object. It is a three-dimensional object characterized in that the deformation that occurs is reduced by the effect of dimensional rules.
  • a three-dimensional object produced by stereolithography has a level of cell compatibility equivalent to that of a commercially available cell culture dish.
  • the present invention opens up the possibility of applying a three-dimensional object produced by stereolithography to a product that requires cell compatibility.
  • the present invention is a key technology that opens up new applications in the biomedical field.
  • FIG. 1 is an explanatory diagram for producing a three-dimensional object by stereolithography.
  • FIG. 2 is a phase contrast microscope image 48 hours after cell seeding.
  • P) is a condition inoculated on a commercially available cell culture dish.
  • “a” indicates a post-cure temperature of 150 ° C. and a heating time of 6 hours (a-1) and 12 hours (a-2).
  • B-1, 2, and 3 have a heating temperature of 175 ° C. and heating times of 6, 12, and 24 hours, respectively.
  • C-1, 2, and 3 have a heating temperature of 200 ° C. and heating times of 3, 6, and 12 hours, respectively.
  • As for the cell growth rate b-3, c-2, and c-3 show the cell growth rate statistically equivalent to P.
  • FIG. 4 is a table of each post cure condition. In the Examples, various post cure conditions are tabulated.
  • FIG. 5 shows the absorbance of water in which the optically shaped object is immersed for 40 hours. Absorption spectra with peaks at around 249 nm and 200 nm are observed in the water in which the optically shaped object not post-cured is immersed.
  • FIG. 6 is a phase contrast microscope image 48 hours after cell seeding.
  • a culture test was performed with d) SCR751, e) SCR701, and f) SCR11120.
  • Subscript 1) has no post cure
  • subscript 2) has seeded cells on a photocurable resin with post cure. It can be seen that post-cure is effective for all resins. All the bars in the photograph are 50 ⁇ m.
  • a three-dimensional object molded by stereolithography is irradiated on a UV lamp for 1 hour to accelerate curing.
  • the three-dimensional object is heat-treated at least at 175 ° C. for at least 24 hours and at least 200 ° C. for 6 hours. At this time, there is no problem even if the heat treatment temperature is higher than the glass transition temperature which is an index of the heat softening temperature of the adopted material.
  • the present invention is directed to a three-dimensional object having a fine structure formed by stereolithography.
  • FIG. 1 The formation method of the three-dimensional object of the present invention is shown in FIG.
  • the procedure of the micro stereolithography is as follows.
  • a 3D modeling model is input to the 1.3D CAD based on the design data.
  • 2. Convert the 3D modeling model into XY plane data of n layers cut by a plane horizontal to the Z axis.
  • 3. The resin is cured by scanning the laser from the first layer on the XY plane. 4. Each time the scanning of the single layer laser is finished, the next uncured resin layer is applied and repeated up to n layers (FIG. 1).
  • the stereolithography produced by the above process was washed in an ultrasonic cleaner for 3 minutes in a Glycol ether ester, and then washed in 99.5% Ethanol for 3 minutes.
  • the stereolithography was then stored in a desiccator.
  • a He-Cd laser (325 nm, KIMMOM KOHA Co., Ltd.) was used as a light source of the micro stereolithography apparatus.
  • Each condition used in the optical modeling was performed with a laser power of 15 mW, a laser scanning speed of 800 mm / s, a scanning interval of 15 ⁇ m, and a stacking interval of 100 ⁇ m.
  • a cell culture container was prepared in order to evaluate cell compatibility in a culture container prepared using the stereolithography.
  • the cell culture container was prepared with an outer diameter of 16 mm, an inner diameter of 15 mm, a bottom surface thickness of 0.8 mm, and a height of 2 mm.
  • Photo-curable resin An epoxy-based general-purpose photo-curable resin (SCR-751, D-Mec: critical exposure 20 mj / cm 2, glass transition temperature after curing 108 ° C.) was used for optical modeling.
  • epoxy-based general-purpose, moisture-resistant photo-curing resin SCR-701, D-Mec
  • the critical exposure amount of this resin is 33 mj / cm2, after curing
  • the glass transition temperature of is 81 ° C.
  • Epoxy water toughness photocurable resin (SCR11120, D-Mec) This resin has a critical exposure of 12 mj / cm 2 and a glass transition temperature of 43 ° C. Three types of resins including these two types were used in a culture test cured with an Xe lamp. In addition to the above, a photocurable material selected from the group consisting of acrylates, epoxies, acrylate / epoxy composites, and oxetanes can be used as the photocurable resin.
  • Cell culture A rat melanoma cell line (PC12, RBC0009, Riken Cell bank, Tsukuba), which is often used as a model cell in the evaluation of neurotoxins, was used 15).
  • the medium used is DMEM (MED-006, IWAKI) + 10% Fetal Bovine Serum + 10% Horse Serum.
  • the cell suspension is adjusted to 5.1 ⁇ 10 2 cells / mm 2 and cultured in an environment of 37 ° C. and 5% CO 2. It was.
  • the positive control was cultured in 96-well MicroWellplate (3860-096, IWAKI).
  • Observation of cells seeded in a culture vessel prepared by micro stereolithography was performed with a phase contrast microscope. Phase images were taken at 3, 4.5 and 6 mm from the center of the bottom of the culture vessel. The cell morphology was observed from this photograph, and the cell density was measured.
  • post-cure method There are two types of post-cure, in which post-processing is performed to completely complete the polymerization reaction: “post-exposure method” applied to mercury lamps after the completion of micro stereolithography and “post-bake method” that promotes curing by raising the environmental temperature. There is.
  • post-cure treatment using both post-exposure and post-bake was performed on the culture vessel prepared by micro stereolithography. Specifically, after the modeling is completed, the Xenon lamp (L2423, Hamamatsu Photonics) is exposed for 1 hour. Thereafter, treatment was further carried out in an oven (DRD360DA, Advantec) at room temperature, 150, 175, and 200 ° C.
  • This culture vessel was post-cured by post-baking for at least 24 hours at the optimum conditions clarified in the previous chapter for at least 24 hours and at least 200 hours at 6 hours.
  • the absorbance of this water was measured using an ultraviolet absorption spectrometer (BioSpec-1600, Shimadzu Corporation) to obtain an absorption spectrum. The absorbance was corrected so that the water absorption spectrum was zero.
  • the optical path length was measured at 1 cm.
  • the substance Since the magnitude of the absorbance peak of the absorption spectrum correlates with the resin volume in the solvent, the substance is presumed to be an eluate from the resin. On the other hand, those absorption spectra were not detected from the optical modeling resin after the post-cure treatment. Since the optical modeling resin used in this experiment has a glass transition temperature of 108 ° C. at which softening starts, there is a possibility of deformation during the post-baking process under load or by its own weight. However, in the micro stereolithography method, a micro structure having a size of several microns to about 1 mm is mainly used. Therefore, the volume force is sufficiently smaller than the surface area force due to the “scale effect”. As a result, thermal deformation is negligibly small.
  • This method can be applied on the micro scale without limitation on the shape of the object.
  • absorption spectra having peaks at around 249 mm and 200 mm are detected from the water immersed in the optical modeling culture vessel that has not been post-cured, and the absorbance increases when the volume of the optical modeling resin increases. The concentration of the product increased (see FIG. 5).
  • these two peaks were not detected from the water immersed in the post-cure optical modeling culture vessel.
  • Each of the three types of photocurable resins was poured into a silicon rubber mold, and a circular plate having a diameter of 16 mm and a thickness of 0.8 mm was exposed and cured with a Xenon lamp. Thereafter, post-baking was performed at 200 ° C. for 6 hours to conduct a cell culture test (FIG. 4: 21-26), and the state of the cells 48 hours after cell seeding was observed with a phase contrast microscope image. (Experimental result) Any kind of epoxy stereolithography resin as a sample was not able to adhere to the plate surface and was killed when a cell culture test was conducted without post-cure (FIG. 6: d-1, e-1, f). -1).
  • Non-Patent Document 14 Report that the cell activity varies depending on the shape of the scaffold made of the optical modeling resin.
  • these reports are not compared with the cell activity obtained by the usual culture method, but only provide one condition for improving the culture results. It should not be compared with the results of this study, which achieved a cytocompatibility comparable to dishes.
  • the post-baking temperature described above exceeds the glass transition point of the optical modeling resin, and there is a possibility that the shape may be deformed in the post-baking process in the case of a loaded state or a structure having a heavy weight.
  • a micro structure of about several microns to 1 mm is mainly produced.
  • Example 1 A three-dimensional cell culture vessel was formed using stereolithography. More specifically, a cell culture container having an outer diameter of 16 mm, an inner diameter of 15 mm, a wall surface height of 2 mm, and a bottom surface thickness of 0.8 mm was formed. At this time, SCR751 (glass transition temperature 108 ° C., Deemec Co., Ltd., Chuo-ku, Tokyo) was used as the material.
  • the produced cell culture vessel was irradiated with a mercury xenon lamp (L2423, Hamamatsu Photonics, Hamamatsu City, Shizuoka Prefecture) for 1 hour in order to promote curing. Thereafter, heat treatment was performed under 18 conditions of temperature conditions 150, 175, and 200 ° C. and heating time conditions of 0.5, 3, 6, 9, 12, and 24 hours, respectively.
  • PC12 cells rat brown seed-derived cell line
  • FIG. 2 at 200 ° C. for 6 hours or more and 175 ° C.
  • the ratio of the number of cells after 48 hours in the cell culture vessel heated for 24 hours and the number of cells immediately after seeding and the ratio of the number of cells after 48 hours on a commercially available cell culture dish separately cultured and the number of cells immediately after seeding are as follows: There was no significant difference when tested statistically. This relationship is indicated by * in FIG. It was shown that cell compatibility was imparted to the cell culture container formed by stereolithography by performing a heat treatment at 200 ° C. for 6 hours or longer.
  • the cell culture vessel molded using the stereolithography method Those subjected to heat treatment for 6 hours and those not subjected to heat treatment were stored in water for 40 hours. Absorption spectra were measured using ultraviolet absorption spectroscopy for water in which these cell culture vessels were stored. As a result, as shown in FIG. 3, the water in which the cell culture vessel formed by the unprocessed stereolithography was immersed had 249 mm, and the peaks shown in 2 of FIG. 3 in the absorption spectrum at wavelengths near 200 nm.
  • the present invention a general-purpose method for imparting cell compatibility to an optically shaped object has been developed and its effectiveness has been shown. According to the present invention, it was quantitatively verified that the stereolithography product has substantially the same level of cell compatibility as a commercially available cell culture dish. In addition, it was clarified by ultraviolet absorption spectroscopy that the composition inside the optically shaped article was changed in the post-cure process, and the cause of the reduction in cytotoxicity was shown. Verification experiments using other photo-curing resins were performed, and it was shown that this method is effective with various resins.
  • the present invention has been described with reference to the embodiments, the present invention is not limited to the above embodiments.
  • the present invention it is possible to design a tailor-made implantable device using a micro-stereolithography method, which has been impossible until now, and to apply cells to microchemical devices such as three-dimensionally arranged cell devices and chemical IC chips. Become. It will be a key technology that will open up new applications in the biomedical field.

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Abstract

L'invention porte sur une structure tridimensionnelle, un objet tridimensionnel qui a été fabriqué par stéréolithographie étant détoxifié pour conférer une cytocompatibilité. La cytocompatibilité fait référence aux propriétés par lesquelles un matériau n'est pas toxique vis-à-vis de cellules et un matériau ne porte pas atteinte aux activités de survie de cellules. Un objet tridimensionnel formé par stéréolithographie est exposé à une lampe UV pendant une heure pour favoriser le durcissement. L'objet tridimensionnel subit un traitement thermique pendant au moins six heures à une température supérieure ou égale à 175°C. Dans ce cas, il est acceptable que la température du traitement thermique dépasse la température de transition vitreuse, qui est un indicateur de la température de ramollissement thermique du matériau en utilisation. L'invention porte sur un objet tridimensionnel ayant une microstructure formée par stéréolithographie. Avec un corps de structure minuscule, le problème de déformation dû à son propre poids pendant un traitement thermique est réduit du fait de la règle de la taille. En conséquence, il n'y a pratiquement pas de variation de taille d'un objet tridimensionnel obtenu au moyen de cette invention avant/après traitement thermique.
PCT/JP2009/068734 2008-10-30 2009-10-26 Objet tridimensionnel fabriqué par stéréolithographie et auquel un traitement de cytocompatibilité est appliqué WO2010050604A1 (fr)

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EP09823714.2A EP2351825B1 (fr) 2008-10-30 2009-10-26 Objet tridimensionnel fabriqué par stéréolithographie et auquel un traitement de cytocompatibilité est appliqué
US12/998,553 US8845948B2 (en) 2008-10-30 2009-10-26 Cytocompatible three-dimensional structures fabricated by microstereolithography

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JP2008279411A JP5114362B2 (ja) 2008-10-30 2008-10-30 光造形法によって作製され細胞適合化処理を施された３次元物体
JP2008-279411 2008-10-30

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